Variants in DENND1A and LHCGR are associated with endometrioid adenocarcinoma

Objective

The aim of this study was to explore the polycystic ovary syndrome (PCOS) related single nucleotide polymorphisms (SNPs) rs13405728 (in gene LHCGR), rs13429458 (in gene THADA) and rs2479106 (in gene DENND1A) in women with endometrial carcinoma.

Methods

We conducted a case-control study comprising 96 Han Chinese women with endometrial carcinoma, and 192 healthy controls. SNPs rs13405728, rs13429458 and rs2479106 were genotyped by polymerase chain reaction (PCR) and direct sequencing. The effects of body mass index (BMI) and age were evaluated using an unconditional logistic regression model adjusted for potential confounders.

Results

The allele frequencies of SNPs rs2479106 and rs13405728 were significantly different (P < 0.05) between endometrial carcinoma group and control group, and the difference was especially significant in the subgroup of endometrioid adenocarcinoma. Genotyping analysis showed that allele G in rs2479106 and allele A in rs13405728 could confer risk to endometrioid adenocarcinoma.

Conclusions

Our results suggest that SNPs rs2479106 in gene DENND1A and rs13405728 in gene LHCGR are associated with endometrioid adenocarcinoma.     

Association of polycystic ovary syndrome susceptibility single nucleotide polymorphism rs2479106 and PCOS in Caucasian patients with PCOS or hirsutism as referral diagnosis

Context

Polycystic ovary syndrome (PCOS) is the most common endocrine disease among premenopausal women. A recent study found association between three single nucleotide polymorphisms (SNPs) and PCOS in a cohort of Han Chinese women.

Objective

To investigate the association between rs13405728 (LHCGR gene), rs13429458 (THADA gene) and rs2479106 (DENND1A gene), PCOS, hirsutism and metabolic and hormonal parameters in a well characterized cohort of Caucasian patients of Danish descendant with PCOS or hirsutism.

Study design

Patients underwent clinical examination, hormone analyses, oral glucose tolerance test and transvaginal ultrasound. Genetic variation was tested using allelic discrimination by real-time PCR.

Patients

268 patients referred to The Department of Endocrinology, Odense University Hospital, Denmark with PCOS or hirsutism between 1997 and 2011. Two hundred and forty-eight healthy females were included as controls.

Results

Genotype distributions and allele frequencies of rs13405728, rs13429458, and rs2479106 were comparable in patients and controls. The rs2479106 G allele was associated with a decreased PCOS susceptibility. None of the SNPs were associated with hirsutism or increased metabolic parameters.

Conclusions

The rs2479106 G allele was associated with decreased PCOS susceptibility, thus confirming previously reported findings of association between rs2479106 and PCOS. Metabolic and hormonal parameters were comparable between genotypes of rs13405728 and rs2479106.     

Association of luteinizing hormone/choriogonadotropin receptor gene polymorphisms with polycystic ovary syndrome risk: a meta-analysis

To investigate the association between Luteinizing hormone/choriogonadotropin receptor (LHCGR) gene polymorphisms and polycystic ovary syndrome (PCOS). A systematic literature search and meta-analysis using STATA software for included studies. Fourteen case-control studies containing rs13405728, rs4539842, and rs2293275 of LHCGR gene were included, which was comprised of 11,738 PCOS cases and 35,329 controls. Results of the meta-analysis showed a significant association between PCOS and rs13405728 (for G vs. A: OR?=?0.735, 95% CI?=?0.699–0.773, p<.001; For GG vs. AG?+?AA: OR?=?0.578, 95% CI?=?0.436–0.767, p<.001; For GG?+?AG vs. AA: OR?=?0.817, 95% CI?=?0.741–0.901, p<.001) in Asian populations, and rs4539842 (for ins/ins vs. ins/non?+?non/non: OR?=?0.686, 95% CI?=?0.483–0.974, p=.035) and rs2293275 (for AA vs. AG?+?GG: OR?=?4.115, 95% CI?=?1.033–16.38, p=.045) in Caucasian populations, respectively. LHCGR gene variations are population specifically associated with PCOS, which indicated these SNPs in LHCGR may contribute to the pathogenesis of PCOS and could be used as potential biomarkers to predict the risk of PCOS.     

The NLRP3 rs10754558 polymorphism is a risk factor for preeclampsia in a Chinese Han population

Objective: Previous studies have indicated that the nucleotide-binding domain, leucine-rich repeat containing protein 3 (NLRP3) inflammasome is activated by monosodium urate in the trophoblast of preeclampsia (PE) patients, leading to augmented placental IL-1β levels. Thus, the purpose of our study was to investigate the association between NLRP3 polymorphisms, rs10754558 and rs2027432, and PE in Chinese Han population.

Methods: The NLRP3 polymorphisms, rs10754558 and rs2027432, were genotyped by real-time PCR in 1024 PE patients and 1194 control subjects. A χ² test was used to compare the genetic distribution between the two groups, and an analysis of variance was used to conduct the genotype–phenotype analysis.

Results: We demonstrated a significant difference in genotypic frequency of the rs10754558 (χ²?=?9.97, p?=?.007) in NLRP3 between PE patients and controls. Additionally, there was a significant difference between cases and controls in the dominant model of G allele (χ²?=?7.70, p?=?.006, odds ratio =0.77, 95%confidence interval 0.64–0.93). What’s more, the genotypes distributions of rs10754558 were found to be associated with both the severe and late onset PE. (χ²?=?8.53 p?=?.01, χ²?=?9.24, p?=?.01.) However, no significant statistic differences were found in the genotypic distributions and allelic frequencies for rs2027432 between two groups (for genotypic distribution, χ²?=?0.17, p?=?.92; for allelic frequency, χ²?=?2.26, p?=?.13, odds ratio =0.90, 95% confidence interval 0.79–1.03).

Conclusions: Our results reveal that NLRP3 may be involved in the development of PE in a Chinese Han population. However, further validation of the associations of other NLRP3 SNPs with PE in other populations is required.     

Vitamin D receptor gene polymorphisms and risk of polycystic ovary syndrome in South Indian women

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of reproductive age women. Emerging evidence suggests that Vitamin D Receptor (VDR) might be a causal factor for characteristics associated with PCOS such as obesity and type 2 diabetes. Present study investigated association between VDR gene BsmI A/G (rs1544410), ApaI A/C (rs7975232) and TaqI T/C (rs731236) single nucleotide polymorphisms and PCOS risk in South Indian women. Genotyping of VDR gene SNPs was carried out in PCOS patients (n?=?95) and controls (n?=?130) by PCR-RFLP method and confirmed by sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D′) for pairwise linkage disequilibrium (LD) were assessed by Haploview software. Results showed significantly increased frequencies of BsmI G/G (p?=?.0197), ApaI C/C (p?=?.048), TaqI C/C (p?=?.044) genotypes and BsmI G (p?=?.0181), ApaI C (p?=?.0092), TaqI C (p?=?.0066) alleles in patients compared to controls. In addition, the frequency of the ‘BsmI G, ApaI C, TaqI C’ haplotype was also significantly elevated in patients (p?=?.0087). In conclusion, the VDR gene BsmI A/G ApaI A/C TaqI T/C and haplotype may constitute an inheritable risk factor for PCOS in South Indian women.     

Haplotype analysis of VEGF gene polymorphisms in polycystic ovary syndrome

Abstract

This study evaluated the association of polymorphisms of VEGF (endothelial vascular growth factor) gene + 936C/T (rs3025039), 1154?G/A (rs 1570360) and ?2578?C/A (rs 699947) in patients with polycystic ovary syndrome (PCOS) and to perform the haplotypes formed by the alleles in the Brazilian population. A total of 110 women without PCOS and 112 women with PCOS were included in the study. Genotyping analyses were performed using the PCR-RFLP assays (rs 3025039 and rs 699947) and by allelic discrimination using the real-time PCR technique (rs 1570360). In the univariate analysis, we observed a significant difference between the groups for the polymorphism rs 1570360 and this polymorphism presented statistical differences between the groups for the recessive model (p?=?.04). The frequency of the T-G-C haplotype showed a statistically significant difference between women with PCOS and controls (p?=?.05). The ?2578?A/C polymorphism was more frequent in the control group, which may be associated with a protective characteristic for the PCOS manifestation. In the sample analysis, polymorphism rs 1570360 is associated with PCOS and the T-G-C haplotype could be associated with protective factors.     

Leutinizing hormone/choriogonadotropin receptor and follicle stimulating hormone receptor gene variants in polycystic ovary syndrome

Purpose

Previous studies identified follicle-stimulating hormone receptor (FSHR) and luteinizing hormone/choriogonadotropin receptor (LHCGR) genes as polycystic ovary syndrome (PCOS) susceptibility loci, which was dependent on the racial/ethnic background of studied population. We investigated the association of genetic variants in FSHR and LHCGR with PCOS in Bahraini Arab women.

Methods

A retrospective case–control study, involving 203 women with PCOS, and 211 age- and ethnically-matched control women. FSHR and LHCGR genotyping was done by allelic exclusion method (real-time PCR).

Results

Significantly lower frequencies of heterozygous LHCGR rs7371084 and FSHR rs11692782 genotype carriers were seen between women with PCOS vs. controls, and increased frequency of heterozygous homozygous LHCGR rs4953616 genotype carriers were detected between women with PCOS compared to control women. Limited linkage disequilibrium was noted among LHCGR and FSHR SNPs, and 2 blocks were constructed: the first (Block 1) spanning 61 kb contained the six tested LHCGR SNPs, and the second (Block 2) spanning 298 kb contained four of the five tested FSHR SNPs. Higher frequency of LHCGR GTCAAG haplotype was seen in women with PCOS compared to controls; the frequencies of the remaining LHCGR haplotypes, and all FSHR haplotypes were similar between cases and controls.

Conclusion

This is the first study to confirm the association of novel LHCGR (rs7371084, rs4953616) and FSHR (rs11692782) SNPs with PCOS. The differential association of LHCGR and FSHR variants with PCOS confirms the racial/ethnic contribution to their association with PCOS.

     

High level of visfatin and the activation of Akt and ERK1/2 signaling pathways are associated with endometrium malignant transformation in polycystic ovary syndrome

Abstract

This study aimed to assess the clinicopathological significance of serum levels and endometrium tissue expression of visfatin in polycystic ovary syndrome (PCOS) patients. A total of 80 PCOS patients and 80 matching controls were included in this study. We analyzed the relationship between the expression of visfatin in endometrium and clinicopathological characteristics in PCOS patients. The correlation between the expression of visfatin and p-Akt, Akt, p-ERK1/2, and ERK1/2 in PCOS tissues was evaluated as well. Visfatin expression in PCOS endometrial tissues were significantly higher than those in controls (p?=?.001). The expression of phosphorylation of Akt and ERK1/2 were significantly higher in PCOS endometrium tissues compared to controls (p?<?.05). Moreover, a high expression of tissue visfatin in PCOS tissues was positively correlated with the expression of p-Akt (p?=?.015), and p-ERK1/2 (p?=?.013). Western blotting revealed that protein expression of visfatin in PCOS patients with endometrial hyperplasia and cancer was higher than that in patients with normal endometrium tissues, and the difference was statistically significant (p?=?.027). The expression of p-Akt (p?=?.018) and p-ERK1/2 (p?=?.035) in PCOS patients with endometrial hyperplasia and cancer was significantly higher than that in patients with normal endometrium tissues. Visfatin may be a potential biomarker for endometrial malignant transformation in PCOS patients.     

Possible effects of lipoprotein-associated phospholipase A2 single-nucleotide polymorphisms on cardiovascular risk in patients with preeclampsia

Purpose: Lipoprotein lipase-associated phospholipase A2 (Lp-PLA2) is a vascular inflammatory marker associated with cardiovascular diseases (CVD). Women with preeclampsia (PE) have elevated vascular inflammation and at higher CVD risk in the later life. We hypothesize that vascular inflammation related genetic variations increase the risk for developing future cardiovascular disease in women with PE. To test this hypothesis, we studied PLA2G7 gene polymorphisms, Lp-PLA₂ mass, activity, index, and other cardiovascular risk factors in women with preeclampsia.

Methods: A total of 200 pregnant women were included into the study. We stratified the PE group: early (28.7?±?3.0 weeks) and late onset (36.0?±?1.4 weeks). Serum Lp-PLA2 mass in the early PE and the late PE group were significantly higher than the control group (p?=?.000). Lp-PLA2 index, Hs-C-reactive protein (CRP), serum amyloid A (SAA), calprotectin, and PTX3 levels were higher in early and late PE (p?=?.000). Single-nucleotide mutations of PLA2G7 rs1805017 (r?=??0.228, p?r?=?0.216, p?Conclusions: Lp-PLA2 genetic variability with vascular inflammatory markers might contribute the incidence of future cardiovascular events.     

Pulmonary edema in preeclampsia: an Indonesian case–control study

Objective: To analyze risk factors, obstetric outcome and the need for mechanical ventilation in preeclampsia complicated by pulmonary edema.

Materials and methods: Case–control study using medical record on preeclampsia complicated by pulmonary edema patients in East Java tertiary referral hospital over 2?years. A simple scoring system was developed to predict the need for mechanical ventilation, using logistic regression.

Results: 1106 cases of preeclampsia were admitted, with 62 cases (5.6%) had pulmonary edema. Postpartum (p?p?=?.001) proportions were higher in the preeclampsia with pulmonary edema group. Of the 62 cases with pulmonary edema, 81% required intensive care admission and 60% needed mechanical ventilation support. Mechanical ventilation used was associated with eclampsia (p?=?.04), hypertensive crisis (p?=?.02), lower serum albumin (p?=?.05) and higher creatinine (p?=?.01). A simple scoring model developed could predict a 46%–99% probability of need for mechanical ventilation (AUC (ROC): 0.856, 95%CI 0.763–0.95).

Conclusions: Pulmonary edema is a common complication of preeclampsia in Indonesian referral hospitals. This severe complication increased maternal and perinatal morbidity and mortality. The developed scoring model in this study can be used as a triage tool to predict the probability of mechanical ventilation use due to this complication.     

CASPASE-8 gene polymorphisms (rs13416436 and rs2037815) are not associated with preeclampsia development in Brazilian women

Background: Preeclampsia is responsible for considerable mortality and morbidity of mother and sibling. The etiology of preeclampsia is still unknown. Family studies indicate the involvement of genes located on chromosome 2 in preeclampsia development. Considering the importance of apoptosis and chromosome 2, one promising candidate for the study of the genetic cause of this syndrome is the CASPASE-8 gene, which was chosen as the subject of this study.

Objective: The aim of this study was to determine the frequencies of the genotypes for CASP8 gene polymorphisms (rs13416436 and rs2037815) and to associate these with preeclampsia development in Brazilian women.

Methods: Women with and without preeclampsia were investigated. Accordingly, peripheral blood was collected and DNA extracted, followed by genotyping using Real-time PCR with hydrolysis probe (Taqman^® Life Technologies).

Results: The results showed no association between genotypes and preeclampsia development for both polymorphisms studied (χ^2?=^?1.03; p?=?0.59, for rs13416436 and χ^2?=^?1.06; p?=?0.58 for rs2037815).

Conclusions: It seems that CASP8 gene polymorphisms (rs13416436 and rs2037815) are not important candidates for the development of preeclampsia. Other genes related to the apoptosis process or other polymorphisms in this gene should be studied in order to understand better the etiology of preeclampsia.     

Genetic variants and clinical relevance associated with gestational diabetes mellitus in Chinese women: a case-control study

Purpose: Gestational diabetes mellitus (GDM) may share similar mechanisms with type 2 diabetes and obesity. In the current study, we aimed to verify twenty genes reported to be associated with type 2 diabetes and obesity in the Chinese GDM population.

Methods: Pregnant women aged 20–49?years at 24–28 gestational weeks were recruited and 556 cases and 445 controls were enrolled in the study. The genotyping of single nucleotide polymorphisms (SNPs) was performed on peripheral blood samples.

Results: We discovered that GDM was associated with rs945508 (OR?=?1.368, 95% CI?=?1.080–1.732, p?=?.009), rs10804591 (OR?=?1.446, 95% CI?=?1.192–1.754, p?p?=?.043) and rs1552224 (OR?=?1.451, 95% CI?=?1.071–1.964, p?=?.016).

Conclusions: We found that four SNPs associated with type 2 diabetes and obesity may also increase the risk of developing GDM in the Chinese population. Among these SNPs, we report for the first time that rs945508 in ARHGEF11, rs10804591 in PLXND1 and rs10245353 in NFE2L3 were associated with GDM.     

Association of the luteinizing hormone/choriogonadotropin receptor gene polymorphism with polycystic ovary syndrome

This study aimed at evaluating possible associations of the single nucleotide polymorphism (SNP) in luteinizing hormone/choriogonadotropin receptor (LHCGR) gene G935A and polycystic ovary syndrome (PCOS) phenotype. The study included 100 PCOS female patients and 60 healthy female control subjects. The patients were recruited from the Gynecology out-patient clinic, Kasr Al-Aini Hospital, Cairo University. All candidates underwent full history taking and clinical examination with calculation of body mass index. Serum and EDTA samples were collected from each patient after a written consent. A hormonal profile was done for each patient as well as DNA analysis of the G935A polymorphism of LHCGR gene. In PCOS group, 26% were homozygous (AA), 27% were heterozygous (GA) and 47% were wild genotype (GG), while in controls 30% were heterozygous and 70% were wild genotype (OR: 2.25; CI: 1.16–4.386; p value: 0.012). The homozygous 935A individuals were at higher risk to develop PCOS than controls (OR: 1.80; CI: 1.54–2.09; p value < 0.001).We found a genetic variant, which is associated with PCOS in a sample of the Egyptian population. These results may provide an opportunity to test this SNP at the LHCGR gene in fertile or infertile women with family history to assess their risk of PCOS.     

The role of FTO variants in the susceptibility of polycystic ovary syndrome and in vitro fertilization outcomes in Chinese women

We investigated the association between single nucleotide polymorphisms (SNPs) in the fat mass and obesity associated (FTO) gene (rs9926289 A/G, rs79206939 A/G, rs9930506 A/G, rs8050136 A/C, and rs1588413 C/T) and polycystic ovary syndrome (PCOS), as well as outcomes of in vitro fertilization (IVF). A case-control study consisting of 147 PCOS patients and 120 healthy controls was conducted. FTO SNPs were genotyped by PCR to determine allelic frequencies, and IVF outcomes were analyzed. The results showed that FTO rs8050136 (p?=?.025) and rs1588413 (p?=?.042) were significantly associated with PCOS susceptibility, and women with risk alleles were often found to be obese (p?p?p?相似文献   

The association between polymorphisms of genes related to inflammation and recurrent pregnancy loss

Aim: Recurrent pregnancy loss (RPL) occurs in 1–2% of pregnant women and about 50% of RPL cases are unexplained. Previous studies have shown that genetic variation in immune response genes can contribute to the risk in pregnancy maintenance during pregnancy. The aim of the present study was to evaluate the relationship between RPL and genes those have previously been associated with an inflammatory process on 107 RPL cases and 187 healthy controls.

Methods: In this work, the single-nucleotide polymorphisms was examined by utilizing the direct sequencing and the Sequenom MassARRAY system.

Results: The FAU rs769440?G allele had higher frequencies in patients with RPL (p?=?.019). No association was observed between other polymorphisms and RPL.

Conclusion: The results showed an association between FAU rs769440 polymorphism and RPL in Chinese Han population.     

Is there a role for kisspeptin in pathogenesis of polycystic ovary syndrome?

Aim: To investigate association of kisspeptin levels in infertile women with different ovarian reserve patterns.

Materials and methods: In this prospective cross-sectional study, 157 participants were recruited. The women were divided into three groups: (i) adequate ovarian reserve (AOR) (n?=?57), (ii) high ovarian reserve (PCOS) (n?=?60), (iii) diminished ovarian reserve (DOR) (n?=?40). Weight, height, waist circumference (WC), hip circumference (HC), body mass index (BMI), waist/hip ratio (WHR) were measured. The blood samples were analyzed for estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), total testosterone (TT), 17-hydroxy progesterone (17OHP), dehydroepiandrosterone sulfate (DHEAS), antimullerian hormone (AMH), kisspeptin measurements.

Results: FSH concentration was higher and AMH concentration was lower in DOR group (p?p?p?=?.001, p?p?=?.003, respectively). The 17OHP level did not differ among the groups (p?=?.15). Women with PCOS possessed the highest kisspeptin level (p?=?.01). The kisspeptin level was negatively correlated with FSH level (r?=??0.18, p?=?.02) and positively correlated with TT and DHEAS levels (r?=?0.17, p?=?.02 and r?=?0.23, p?=?.003, respectively).

Conclusions: Women with PCOS had increased serum kisspeptin levels. Kisspeptin concentrations were negatively correlated with serum FSH and positively correlated with serum TT and DHEAS levels.     

Maternal serum glycodelin levels in preeclampsia and its relationship with the severity of the disease

Purpose: Preeclampsia, in which insufficient trophoblastic invasion is thought to be one of the underlying mechanisms, is a common pregnancy disorder. Glycodelin is a regulator of immunosuppression, fertilization, implantation, and placentation. Because of its inhibitory effects on trophoblastic activity, trophoblast invasion is disturbed when its levels alter. We aimed to analyze serum glycodelin levels in preeclampsia and evaluate whether it correlates with the severity of disease.

Methods: This is a prospective case–control study conducted in a research and training hospital between March and September 2016. In this study, a total of 55 preeclamptic and 65 healthy pregnants were included. Preeclamptic patients were divided into two subgroups: 25 severe and 30 mild. Maternal serum glycodelin levels were measured using enzyme-linked immunosorbent assay.

Results: Glycodelin levels were higher in preeclamptic group as compared with controls (71.38?±?22.78 versus 42.32?±?12.28?ng/ml, p?p?r?=?0.637 and r?=?0.714, respectively, p?r?=?0.369, p?=?.006 and r?=?0.377, p?=?.005) and proteinuria (r?=?0.342, p?=?.011). Moreover, it was correlated with birth weights and gestational age at delivery (r?=??0.386, p?=?.004 and r?=??0.394, p?=?.003, respectively). The role of glycodelin to diagnose preeclampsia was evaluated by receiver operating curve (ROC) curve. Area under the curve for glycodelin is 0.897 with p?53.64?ng/ml. Moreover, area under the curve for glycodelin to diagnose severe preeclampsia is 0.788 with p?83.97?ng/ml.

Conclusion: Glycodelin may be a promising marker in predicting the presence and severity of preeclampsia.     

Fertility management experiences of women with polycystic ovary syndrome in Australia

Abstract

Background: Women with polycystic ovary syndrome (PCOS) are usually told that the condition is associated with fertility difficulties. However, little is known about their fertility management including contraceptive use, childbearing desires, and pregnancy outcomes.

Aim: To compare the fertility management experiences and outcomes of Australian women with and without PCOS.

Method: The 2013 Australian electoral roll was used to identify a random sample of 18- to 50-year-old women who were sent the Understanding Fertility Management in Australia survey to be completed anonymously. Factors associated with fertility management and outcomes were identified in multivariable analyses.

Results: Among the 1543 women who completed and returned the survey, 113 (7.3%) reported having PCOS. Women with PCOS reported a similar rate of current contraceptive use as women without PCOS (50.4% vs. 52.6%, p?=?.66). However, they were significantly younger at first pregnancy (24.9 vs. 26.8 years, p?=?.015), more likely to have consulted a health professional about fertility management (OR: 3.86, 95% CI: 2.50–5.96, p?<?.001), and perceive that it would be difficult to conceive (OR: 2.31, 95% CI: 1.41–3.79, p?=?.001) than women without PCOS. There were no significant differences in the number of desired children, unintended pregnancies, live births, abortions or miscarriages between women with and without PCOS.

Conclusion: These findings indicate that women with PCOS need more nuanced information about their fertility potential. While they may experience fertility difficulties because of their condition, they should also be informed that they can conceive spontaneously and need reliable contraception to avoid pregnancy when it is not wanted.     

Maternal/fetal eNOS-Glu298Asp genotypes and their influence on the severity,prognosis, and lipid profile of preeclampsia

Objectives: To analyze the contribution of maternal eNOS-Glu298Asp genotypes and also the association with fetal genotypes to the development of preeclampsia, prognosis, and maternal dyslipidemia.

Methods: Sixty-nine pairs of preeclamptic mothers/newborns and 94 pairs of normotensive mothers/newborns were genotyped for eNOS-Glu298Asp using PCR-RFLP methods.

Results: Women carriers of at least one Asp298 allele had a 1.53-fold (p?=?NS), 1.88-fold (p?=?NS), and 2.08-fold (p?=?.05), respectively, increased risk to develop PIH, mild, or severe preeclampsia. If both the mother and the newborn were carriers of the Asp298 allele, the risk for preeclampsia was 5.09-fold higher (p?p?=?.02) and LDL (mg/dl, 194.9?±?42.8 versus 144.98?±?54.84, p?=?.04) levels and lower HDL levels (mg/dl, 32.12?±?5.48 versus 57.84?±?20.59, p?=?.02) compared to noncarriers. Also, higher LDL levels (mg/dl, 188.76?±?46.61 versus 136.75?±?41.85, p?=?.03) and lower HDL levels (mg/dl, 32.8?±?5.64 versus 61.06?±?22.45, p?=?.02) were found in preeclamptic women with severe preeclampsia whose newborns were carriers of the Asp298 allele.

Conclusions: The eNOS-Glu298Asp variant (in mothers and newborns) in association with dyslipidemia could affect bioavailability of NO and could represent an increased risk for preeclampsia.     

Association of Calpain (CAPN) 10 (UCSNP-43, rs3792267) gene polymorphism with elevated serum androgens in young women with the most severe phenotype of polycystic ovary syndrome (PCOS)

Abstract

Objectives: To highlight a possible association of Calpain (CAPN 10) gene UCSNP-43 polymorphism with hormonal and metabolic traits of young women with different phenotypes of polycystic ovary syndrome (PCOS).

Design: PCOS women were genotyped for the CAPN 10 gene UCSNP-43 polymorphism. A comparison of clinical and biochemical features of women with PCOS stratified on the basis of the CAPN 10 gene UCSNP-43 variants was assessed.

Methods: Anthropometric, hormonal and biochemical measurements were carried out in 668 PCOS women and 200 healthy controls. Subjects were also genotyped for the CAPN 10 gene UCSNP-43 polymorphism. The genotype frequency distributions between groups and controls were compared using the chi-square test. The association of the polymorphism with the clinical and biochemical features of the study cohort was estimated as well.

Results: No association of the frequency of CAPN 10 gene UCSNP-43 polymorphism with PCOS was detected. No association of the polymorphism with the anthropometric, biochemical and hormonal features was detected both in PCOS and control women. The polymorphism was associated with serum Δ4 androstenedione (p?=?0.018), as well as with 17-OH progesterone (17-hydroxyprogesterone) among women with PCOS phenotype A (p?=?0.012).

Conclusions: CAPN 10 gene polymorphism UCSNP-43 is deprived of a metabolic contribution to cardiovascular disease (CVD). However, due to its association with androgen excess in phenotype A, CAPN 10 gene polymorphism UCSNP-43 could be used as a genetic marker for CVD in young PCOS women.